Low frequency of amino acid alterations following therapeutic immunization with HIV-1 Gag p24-like peptides.

Abstract

OBJECTIVES:

In chronic HIV-1 infection, the efficacy of a cellular immune response may decline if the virus evolves into variants not recognized by host immune response. The aim of this study was to explore HIV-1 immune escape mutations imposed by therapeutic immunization by investigating sequence variations that might contribute to relapse of viremia in an immunized, HIV-1-infected cohort.

DESIGN:

We have previously immunized HIV-1-infected individuals on antiretroviral therapy (ART) with a mixture of four short peptides (Vacc-4x) corresponding to p24. Long postimmunization periods without ART allowed longitudinal sequence studies of regions corresponding to Vacc-4x.

METHODS:

Regions of gag p24 including the locations of the Vacc-4x peptides, were sequenced before start of ART, and after postimmunization ART stop (n = 27). Rates and locations of amino acid substitutions were then related to peptide-specific T-cell responses and known epitopes presented by Vacc-4x.

RESULTS:

The overall rate of amino acid substitutions was low during 35 months (median) of postimmunization viremia, with similar rates of substitution within the regions corresponding to Vacc-4x peptides and other p24 regions despite durable Vacc-4x-specific T-cell responses. Postimmunization amino acid substitutions within Vacc-4x regions were detected in only six patients, and only two of them had measurable T-cell responses against the relevant peptide.

CONCLUSIONS:

The results suggested low prevalence of evolutionary selection of p24 despite new and long-lasting Vacc-4x-specific T-cell responses. The conserved Vacc-4x sequences might therefore be particularly suited for therapeutic immunization. Generally, studies of longitudinal sequence variations after immunization might be valuable when assessing immune escape in HIV vaccine trials.

• Authors: Anne-Marte B Kran, Tom Oystein Jonassen, Maja A Sommerfelt, Gunilla Løvgården, Birger Sørensen, Dag Kvale
• Journal: AIDS (London, England) (AIDS) Vol. 24 Issue 17 Pg. 2609-18 (Nov 13 2010) ISSN: 1473-5571 [Electronic] England
• PMID: 20935558 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• AIDS Vaccines
• HIV Core Protein p24
• Peptides

Topics

• AIDS Vaccines (administration & dosage)
• CD4-Positive T-Lymphocytes (immunology)
• Female
• HIV Core Protein p24 (immunology)
• HIV Infections (drug therapy, immunology)
• HIV-1 (immunology)
• Humans
• Male
• Peptides
• Prospective Studies
• Viremia (immunology)